We are requesting funding to purchase a versatile, high sensitivity high-throughput system consisting of an HPLC-chip interfaced to a triple quadrupole mass spectrometer. This instrument will be located in the Biomarker Mass Spectrometry Facility Core in the Department of Environmental Sciences and Engineering of the University of North Carolina at Chapel Hill (UNC-CH), which is a shared facility that serves researchers from the entire university and beyond. This instrumentation will provide us with at least an order of magnitude higher sensitivity than the existing instrumentation. This will allow detection and quantitation of analytes that are present at levels too low for our current instrumentation, and/or where the total amount of sample available precludes analysis with our current instrumentation. The equipment of choice is an Agilent 1200 series nanoflow HPLC interfaced via a 1260 Infinity Chip Cube with an Agilent 6490 LCMS Triple Quadupole mass spectrometry system. This combination is the most sensitive LC-MS/MS on the market, and will allow quantitation of biomarkers of interest with the smallest mass and volume of sample. The Chip Cube interface is also very well suited for use in a shared instrument facility where trace-level analysis is very easily compromised by cross-contamination. This equipment will support nine NIH- funded researchers. PUBLIC HEALTH RELEVANCE: The Biomarker Mass Spectrometry Facility provides accessible routine service for measuring small molecules and biomarkers to the University of North Carolina at Chapel Hill biomedical research community. The LCMS/MS system requested for the Biomarker Mass Spectrometry Facility will enable the Facility to extend by at least an order of magnitude the sensitivity of assays for small molecules, DNA adducts, DNA-protein crosslinks, and other biomarkers in complex biological matrices. This will enhance studies by nine NIH-funded researchers at the UNC-CH School of Public Health and School of Medicine, including three physicianscientists, who address critical health problems related to cancer, cystic fibrosis and other respiratory disease and drug abuse.